Changes In Prolactin Secretion Research Articles

Age-related changes in prolactin secretion and the population of mammotrophs in the rat: A longitudinal study

The concentration of prolactin (PRL) in the blood increases with aging in the rat, and pituitary prolactinomas often develop in aged female rats. We measured blood PRL levels in the course of development of hyperprolactinemia and prolactinomas in individual rats by serial sampling of the blood of living rats. The pituitaries were examined upon the death of the rats to detect prolactinomas by immunocytochemical staining. Hyperprolactinemia in rats without pituitary tumors was inevitably followed by the development of a prolactinoma within 3 months. Rats which had no tumors at the time of death had low PRL levels throughout their lifespan. Counting of anterior pituitary cells after immunocytochemical staining for electron microscopy indicated that the number of mammotrophs increased and that the number of somatotrophs decreased in rats with hyperprolactinemia. Based on these results, we conclude that age-related hyperprolactinemia in female rats represents a precancerous state for prolactinoma.

Temperature Effects on Serum Prolactin Concentrations and Activity of Dopaminergic Neurons in the Infundibulum/Pituitary Stalk of Calves

The effects of ambient temperature on serum concentrations of prolactin and neurochemical estimates of activity of dopaminergic neurons projecting to the infundibulum/pituitary stalk were investigated in Holstein bull calves. Accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the infundibulum/pituitary stalk after intravenous injection of a decarboxylase inhibitor was used to estimate activity of these dopaminergic neurons. Increasing ambient temperature from 21 to 33 degrees C for 22 hr increased serum concentrations of prolactin and decreased activity of the dopaminergic neurons. Conversely, reducing ambient temperature from 22 degrees C to 11 degrees C decreased serum concentrations of prolactin and increased activity of these dopaminergic neurons. It is suggested that alterations in activity of dopaminergic neurons terminating in the infundibulum/pituitary stalk of bull calves may mediate acute temperature-induced changes in secretion of prolactin.

The rate of increase not the amplitude of cytosolic Ca 2+ regulates the degree of prolactin secretion induced by depolarizing K + or hyposmolarity in GH 4C 1 cells

Depolarizing K + and medium hyposmolarity caused striking rises in both cytosolic free Ca 2+ concentration ([Ca 2+] i) and prolactin (PRL) secretion in GH 4C 1 cells, which were completely blocked by removal of medium Ca 2+. However, the increase in [Ca 2+] i and PRL secretion induced by hyposmolarity was clearly slower than that induced by K +. Although there was a good correlation between the zenith of PRL secretion and [Ca 2+] i induced by various intensities of K + or hyposmolarity, the regression slopes were significantly different between the K +- and hyposmolarity-induced changes (P<0.01). There was a good correlation between the maximum rate of change in PRL secretion and that of the increase in [Ca 2+] i when the data from the 2 secretagogues were combined (r=0.994, P<0.001, N=9). We suggest that the rate of increase in [Ca 2+] i may be more important than the amplitude of [Ca 2+] i in stimulating PRL secretion.

Vasoactive intestinal polypeptide-like immunoreactivity during reproduction in doves: Influence of experience and number of offspring

To assess the possibility that vasoactive intestinal polypeptide (VIP) plays a role in naturally occurring changes in prolactin secretion in ring doves, we used immunohistochemical techniques to measure VIP-like immunoreactivity in the brain as a function of stage of the reproductive cycle. Differences between parental and nonparental birds in VIP profiles were detected in the ventral portion of the infundibular region. More specifically, there is an increase in cell size and staining intensity in the ventral infundibulum of breeding birds compared to simultaneously processed tissue taken from control animals. In both sexes, an increase in size of VIP-like immunoreactive cells is detectable during courtship and early incubation, anticipating the increase in plasma prolactin levels. VIP cell size remains elevated from about Incubation Day 14 to Brooding Day 14, and a steady decrease is observed during the remaining posthatching period, as squab begin to feed independently. Compared to parents rearing one squab, those with two young have a prolonged interval of increased infundibular VIP immunoreactivity. Furthermore, doves with no previous experience of a breeding cycle exhibit prolonged VIP-like immunoreactivity compared to experienced parents, paralleling previously described differences between these groups in parental behavior.

The physiology and mechanisms of the stress-induced changes in prolactin secretion in the rat

It is well known that stress in a number of forms induces the secretion of prolactin (PRL) in a number of species. What is not well known is that under certain conditions stress will also induce a decrease in PRL secretion. The conditions whereby stress decreases PRL are those where PRL secretion is elevated such as during the proestrous afternoon surge and during the nocturnal surge of pseudopregnancy. The physiologic significance of the stress-induced increase of PRL is suggested to be important in maintaining the competence of the immune system. The significance of the stress-induced decrease of PRL does not appear to have a major consequence on the physiology of reproduction in the rat and it is suggested that future studies be directed towards its significance in the immune system. The literature is reviewed dealing with the regulation of PRL secretion with emphasis on the factors that generate PRL surges in the rat. In addition the mechanism(s) of the stress-induced increase and decrease is (are) also examined. A hypothesis is presented suggesting an interaction between tuberoinfundibular dopamine secretion and a hypothalamic prolactin releasing factor in the generation of PRL surges and the differential effects of stress on PRL secretion.

Neuroendocrine Function in Transgenic Male Mice with Human Growth Hormone Expression

The neuroendocrine effects of human growth hormone (hGH) secretion were studied in adult male mice into which an hGH gene fused with mouse metallothionein 1 (mMT-1) promoter had been introduced. Intact transgenic mice had significantly greater plasma luteinizing hormone (LH) levels than did normal littermate controls. Castration increased LH levels in normal mice but was without effect on plasma LH levels in the transgenic mice. In vitro LH secretion and pituitary LH content were higher in the intact transgenic mice than in intact controls, while there was no significant difference in pituitary LH levels and in vitro LH secretion between the 2 groups of castrate animals. Intact transgenic mice exhibited a greater median eminence (ME) norepinephrine (NE) turnover than control animals, but ME NE turnover did not increase after castration in the transgenic animals as was the case in control mice. Castrate mice expressing the hGH gene had plasma levels of prolactin (PRL) similar to those seen in castrate controls, which was unexpected based on a previous study showing greatly attenuated PRL levels in intact hGH mice when compared to intact controls from the same line. Dopamine (DA) turnover in the ME was not significantly affected by the presence of the hGH gene, suggesting that the difference in plasma PRL levels between normal and transgenic mice is mediated through changes in PRL-regulating factors other than DA. In conclusion, the expression of the mMT-1/hGH hybrid gene in male mice leads to major alterations in LH secretion and lesser changes in PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of sexual receptivity on LH, FSH and prolactin release after GnRH administration in female rabbits

The influence of sexual receptivity on the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) after i.m. administration of gonadotropin releasing hormone (GnRH) was studied in 23 rabbits of the California strain. Does showing a high or medium sexual receptivity exhibited a clear dose response LH curve, but the low sexual receptivity does did not. LH reached maximum values 15 min after administration of either dose of GnRH. A second peak was found in high sexual receptivity does 165 min after GnRH administration. There was a FSH peak associated with high sexual receptivity, whereas no response was observed associated with low sexual receptivity. In 46% of the animals tested, LH and FSH peaks were seen. A decrease in plasma PRL level was observed in high sexual receptivity does after GnRH administration, together with a clear increase in low sexual receptivity females. The results indicate that changes in PRL secretion could be responsible for the low magnitude of LH and FSH responses to GnRH seen in lactating rabbits which exhibit low sexual receptivity.

Prolactin secretion after hypophysial stalk transection in prepuberal beef heifers

Hypothalamic regulation of prolactin secretion was investigated in crossbred beef heifer calves. Heifers were randomly assigned to hypophysial stalk transected (HST, n = 5) or sham-operated control (SOC, n = 2) groups and were fitted 1 day before surgery with an indwelling external jugular catheter. Prolactin (PRL) in peripheral plasma was measured by radioimmunoassay in samples obtained before, during and after HST or SOC. HST heifers were given thyrotropin-releasing hormone (TRH) 72 h after surgery and again 11 months later. HST heifers were also given haloperidol and α-methyl- p-tyrosine (αMT) 13 and 14 days after surgery. Two HST and three intact heifers were recatheterized 4 and 10 months after HST, and blood was collected over 48 h to determine PRL profiles during the summer and winter. Prolactin was elevated during surgery in both HST and SOC calves. After SOC, PRL declined rapidly and remained low during recovery from surgery and over the next 14 days. In contrast, PRL remained elevated ( P < 0.05) after HST for at least 14 days as compared with SOC. HST calves responded to i.v. injection of TRH 72 h after surgery with an acute increase in PRL ( P < 0.05) within 10 min. HST calves did not respond to i.v. injection of haloperidol or αMT 2 weeks after surgery. Within 4 months after surgery, HST heifers had lower basal PRL levels than observed in intact heifers, and seasonal changes in PRL secretion were also attenuated by HST. HST heifers did, however, remain capable of spontaneous pulses of PRL secretion and responsive to TRH injection 11 months after HST. The results of this study clearly indicate that basal PRL secretion is tonically inhibited by the hypothalamus in prepuberal beef heifers. Furthermore, the inability of HST heifers to respond to administration of αMT and haloperidol indicates that dopamine may play an important role in hypothalamic regulation of PRL secretion in this species.

Interactions of Sex Steroid Hormones and Prolactin in Male and Female Song Sparrows, Melospiza melodia

Subcutaneous implants of estradiol in female song sparrows, Melospiza melodia, maintained sexual receptivity throughout the breeding season. Parental behavior apparently was not affected. Estrogenized females continued to incubate and feed young Plasma levels of prolactin were also unaffected by estrogen treatment. Male song sparrows mated to estrogenized females maintained high levels of testosterone throughout much of the breeding season. Only in late June and early July were testosterone levels in experimental males similar to those of controls. By July, however, levels of testosterone were again elevated significantly over those of controls. These data agree with other investigations showing that continual exposure of males to sexually receptive females maintains high levels of testosterone. The rise in prolactin in males was not affected by high circulating concentrations of testosterone, and changes in prolactin levels throughout the breeding season in experimental males were similar to the control cycle. It is concluded that in the song sparrow, elevated levels of prolactin during breeding do not inhibit secretion of sex steroids, nor do experimentally induced high circulating titers of sex steroid hormones alter seasonal changes in prolactin secretion.

Superfusion and static culture techniques for measurement of rapid changes in prolactin secretion

This chapter describes a superfusion method for the cultured monolayers of anterior pituitary cells that permits the analysis of interactions among various regulatory factors, allows the monitoring of the temporal patterns of hormone release, and is compatible with the simultaneous determination of biochemical and structural changes correlated with secretion. The secretion of prolactin (PRL) is under the regulation of both inhibitory and stimulatory hypothalamic hormones. Dopamine (DA), a well characterized inhibitory hormone, tonically suppresses PRL secretion. The multifactorial regulation of PRL secretion represents a specific but not unique process, in which the sequence and duration of exposure to multiple hypothalamic hormones determine the secretory response. The culture/superfusion technique that is described for dissociated cells permits the unraveling of the hierarchy of the hypothalamic regulation of the secretion of anterior pituitary hormones. Both rapid changes in hormone secretion and cellular events––that is, events occurring within minutes––and slower modulatory effects––that is, effects taking days––can be correlated by the coupling of perifusion techniques with those of cell culture.

Different Dopaminergic Control of Plasma Luteinizing Hormone, Follicle-Stimulating Hormone and Prolactin in Ovulatory and Postmenopausal Women: Effect of Ovariectomy

The main aim of this study was to evaluate the effect of dopamine infusion on plasma luteinizing hormone (LH), follicle-stimulating hormone, (FSH) and prolactin (PRL) after acute (1 week postovariectomy) and chronic (postmenopausal women) estrogen withdrawal. We also studied the same group of postmenopausal women after ovariectomy to evaluate the possible influence of other gonadal factors on the endocrine effects of dopamine. In order to have a further indication of neuroendocrine dopamine activity on pituitary secretions, we measured the change in plasma LH, FSH and PRL after the administration of metoclopramide, a dopamine receptor antagonist. Our findings confirm that in fertile women dopamine infusion inhibits plasma LH and FSH levels and show that 1 week after ovariectomy the LH decrease during dopamine administration is still present whereas the FSH decrease is not. In all groups of patients, dopamine significantly inhibited plasma PRL levels. Metoclopramide increased plasma LH levels in reproductive-age women before ovariectomy, but not in postmenopausal women. Plasma FSH levels did not change in any group and PRL levels increased after metoclopramide administration in all subjects. The present findings show that dopamine regulation of LH is impaired in long-term menopause, but not shortly after ovariectomy. These changes in LH control are not followed by similar changes in PRL secretion, which remains under tonic inhibitory regulation by dopamine. The different behavior of LH and FSH after ovariectomy and in postmenopause shows the independence of LH and FSH regulation.

Drug-induced changes in prolactin secretion. Clinical implications.

Prolactin secretion is affected by various diseases as well as by many drugs in humans and animals. While marked hyperprolactinaemia suggests the presence of a pituitary tumor, moderate changes may also occur in various endocrine or non-endocrine disorders. Drugs can interfere with prolactin regulation via complex mechanisms at the hypothalamus or at the pituitary site, but possible changes in prolactin metabolism are poorly understood as yet. This survey of the literature up to June 1986 covers the influence of various groups of drugs and agents on the plasma prolactin level under various conditions. It contains information that will facilitate evaluation of whether hyper- or hypoprolactinaemia may result from therapeutic intervention or must be related to an underlying disease. It is obvious that more subtle changes can be revealed by the use of dynamic tests either to stimulate or to suppress prolactin secretion.

Prolactin secretion in cattle as affected by haloperidol and α-Methyl- p-Tyrosine

Prolactin (PRL) secretion in response to i.v. injection of different doses of α-Methyl- p-Tyrosine (αMT) and haloperidol (HAL) was studied in one cow and three bulls. HAL was tested at doses of 0.033, 0.1, and 0.33 mg/kg body weight (BW), and αMT was tested at doses of 0.1, 1.0, 10, and 30 mg/kg BW. Blood was collected via an indwelling catheter into the external jugular vein, and plasma PRL was analysed by radioimmunoassay. Dose-related increases in plasma PRL concentrations were observed after administration of both αMT and HAL. Peak PRL concentrations after injection of HAL at a low, medium, and high dose were 22, 45, and 70 ng/ml, respectively. Peak PRL concentrations after injection of increasing doses of αMT were 3.0, 10, 40 and 70 ng/ml. HAL (0.1 mg/kg BW) and αMT (10 mg/kg BW) were administered intravenously to four heifers during summer and winter. Response to both drugs, as measured by changes in PRL secretion, was greater in summer than winter. Peak plasma PRL levels after HAL injection were 327 ± 58 ng/ml in June and 149 ± 27 ng/ml in January, whereas peak levels after αMT were 166±29 and 60±9 ng/ml, respectively. Basal PRL secretion was also greater in summer than winter. The results of this study demonstrate that PRL in peripheral plasma of cattle is increased in response to administration of antidopaminergic drugs and that this increase is greater during the summer than the winter.

Effects of preoptic injections of gastrin, cholecystokinin, secretin, vasoactive intestinal peptide and PHI on the secretion of luteinizing hormone and prolactin in ovariectomized estrogen-primed rats

The effects of intracerebral injections of brain-gut peptides in the preoptic region on the secretion of luteinizing hormone (LH) and prolactin (PRL) were examined in ovariectomized, estrogen-primed rats. Gastrin or cholecystokinin-octapeptide injection in the preoptic region induced a moderate increase of circadian rise of LH secretion in some animals but no appreciable change in PRL secretion. Secretin injection was strikingly effective in increasing circadian rise of LH and PRL secretion. Vasoactive intestinal peptide injection completely abolished the occurrence of circadian rise of LH secretion whereas PHI injection facilitated LH secretion undergoing the circadian rhythm. The results suggest that those peptides act as neurotransmitters or neuromodulators in the preoptic region and are implicated in the regulation of LH and PRL secretion.

Transient increase in prolactin secretion following hypothalamo-pituitary disconnection in ewes during anoestrus and the breeding season.

Hypothalamic control of prolactin secretion was studied in ovariectomized ewes by comparing the effects of hypothalamo-pituitary disconnection (HPD) and sham-operation (sham-HPD). HPD caused a two-fold increase in plasma prolactin concentrations on days 1 and 7 following surgery during anoestrus and a tenfold increase during the breeding season. Thereafter, concentrations gradually declined to be similar to those in sham-HPD ewes by day 43 (breeding season) and day 145 (anoestrus). The maximum plasma prolactin response to HPD was similar during the two seasons (anoestrus: 128 +/- 15 bs breeding season: 118 +/- 13 micrograms/l). Sham-HPD had no effect on plasma prolactin concentrations. Prolactin pulse frequency was not affected by HPD, but increases in plasma prolactin concentrations were associated with increases in pulse amplitude. At the time of the normal anoestrus, plasma prolactin concentrations rose in both the HPD and sham-HPD ewes, raising the question of extra-hypothalamic regulation of seasonal changes in prolactin secretion. Plasma LH and FSH concentrations became undetectable in HPD ewes but were unaltered in sham-HPD ewes. We conclude that hypothalamic inhibition of pituitary prolactin secretion in the sheep can be demonstrated by HPD but that this effect is not sustained. This transience may indicate the additional requirement of hypothalamic-releasing factors in the control of prolactin release. In addition, the surgically isolated ovine pituitary of the HPD animal has an inherent pulsatile secretion of prolactin.

Prolactin secretion in epileptic subjects treated with phenobarbital: sex differences and circadian periodicity.

Circulating basal prolactin (PRL) levels were evaluated in 126 subjects of both sexes with partial or generalized epilepsy, who were treated with phenobarbital (PB) alone or in combination with either phenytoin or benzodiazepines. A significant increase in PRL levels was observed in male, but not in female, patients compared with a sex- and age-matched healthy volunteer group. Circadian PRL secretion, studied in six male epileptic patients on PB monotherapy and in nine normal subjects, showed comparable 24-h PRL mean values and a preserved PRL surge during the night in both groups; however, a statistically significant additional peak was found in male epileptic subjects during the late afternoon. The cosinor analysis of the data, used to evaluate PRL rhythmicity, showed a disruption of the 24-h periodicity in epileptic subjects, while the 12-h periodicity was maintained. These results indicate that central and/or peripheral mechanisms involved in PRL secretion control are more sensitive to PB alone or in combination with other antiepileptic drugs in male than in female subjects. However, the changes of PRL secretion we found were small and unrelated to the different clinical conditions.

The interaction of the medial preoptic area and the dorsomedial-ventromedial nuclei of the hypothalamus in the regulation of the mating-induced release of prolactin.

The medial preoptic area (MPOA) and the dorsomedial-ventromedial nuclei (DMN-VMN) of the hypothalamus regulate the mating-induced nocturnal and diurnal surges of prolactin in rats. The neural mechanisms governing the release of the two surges differ. For the nocturnal surge the MPOA serves an inhibitory role while the DMN-VMN serves a stimulatory role. The diurnal surge is controlled by both areas functioning as stimulatory centers. The goal of the present study was to explore the possibility of functional interactions between the MPOA and the DMN-VMN in control of mating-induced prolactin secretion. Stimulation of the MPOA in conscious, cervically stimulated (CS) females suppresses the nocturnal surge of prolactin. To determine if the inhibitory effects of the MPOA operate through the DMN-VMN, electrical stimulation was applied to the MPOA of conscious ovariectomized female rats bearing bilateral electrolytic lesions of the DMN-VMN. In the first experiment, control (sham-stimulated, sham-lesioned) CS females exhibited normal nocturnal surges which peaked at 03.00 h. MPOA stimulation (01.00-05.00 h) of both sham-lesioned and DMN-VMN lesioned CS females inhibited the release of their nocturnal surges. This suggests that the inhibitory function of the MPOA is independent of the DMN-VMN. MPOA stimulation can induce the release of a diurnal surge if the females are anesthetized with pentobarbital. In the second experiment, MPOA stimulation (15.00-19.00 h) of sham-lesioned anesthetized females produced elevated prolactin levels with significant peaks at 15.30 and 19.00 h. Anesthetized females with DMN-VMN lesions did not respond to MPOA stimulation with any change in prolactin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of binding and pinealectomy on photoperiod and seasonal variations in secretion of prolactin in cattle.

The role of the eyes and pineal gland on photoperiod- and season-induced changes in secretion of prolactin were studied in male cattle. Increasing exposure to light from 8 to 16 hr each day increased basal and thyrotropin-releasing-hormone-induced secretion of prolactin 3.7- and 4.1-fold in three sham-pinealectomized steers. In contrast, basal and thyrotropin-releasing-hormone-induced increases in secretion of prolactin did not change in four blind bulls and were markedly suppressed in three pinealectomized steers when exposure to light was increased from 8 to 16 hr/day. There was no diurnal variation in secretion of prolactin regardless of photoperiod or surgical treatment. However, seasonal changes (averaged 46 ng/ml in June-Aug vs 7 ng/ml in Dec-Feb) in secretion of prolactin persisted in blind and pinealectomized steers previously shown to be nonresponsive to changing photoperiods. Ambient temperature and photoperiod account for most, but not all, of the seasonal variation in secretion of prolactin. We hypothesize there is an endogenous annual rhythm in the secretion of prolactin in cattle.

Thyroid Stimulating Hormone and Prolactin Secretion: Reduced Sensitivity to TRH-Stimulated Prolactin Release after Midpregnancy in Rats

Prolactin (PRL) and thyroid stimulating hormone (TSH) plasma concentrations were measured during the latter part of the dark period in early and mid-late pregnancy in the rat. On Days 4-5 and 7-8 of pregnancy, plasma PRL concentrations surged between 22:00 and 06:00 hr and TSH values increased between 22:00 and 02:00 hr. While the TSH pattern was maintained during the second-half of pregnancy, surges in PRL release ceased and PRL levels remained at less than 10 ng/ml. The effects of thyrotropin releasing hormone (TRH) administration on PRL and TSH secretion were then measured to determine whether the second-half of pregnancy is associated with a decrease in sensitivity to an agent that can stimulate PRL release. Injection (iv) of cannulated pregnant rats with a low dosage (20 ng) of TRH stimulated a twofold increase in plasma TSH during both early (Days 5-9) and later (Days 14-18) pregnancy but did not change plasma PRL levels. Treatment with a high dosage (2 micrograms) of TRH induced a sixfold rise in plasma TSH during both phases of gestation. The higher dose of TRH also stimulated elevations in plasma PRL during early and mid-late pregnancy; however, both the absolute increase in the amount of PRL in plasma and the percentage increase over baseline levels were greater from Days 5-9 than from Days 14-16 of gestation. These data indicate that the neuroendocrine sensitivity to factors that stimulate PRL secretion changes as pregnancy progresses, and suggest that nocturnal secretion of PRL and TSH during pregnancy may be regulated, in part, by a common trophic factor.

Effects of thyroid hormones and prolactin on food intake and weight changes in young male reindeer (Rangifer tarandus tarandus)

Yearling male reindeer were treated with thyroid hormones and prolactin to see if reported seasonal variations in these hormones could participate in the control of the growth cycle in Cervidae. Both prolactin and thyroid hormone injections were followed by increased food intake. The effect was not additive, and no interactions were seen. Weight gain decreased after treatment with thyroid hormone, alone or in combination with prolactin. Weight gain increased in animals treated with prolactin alone. We conclude that changes in prolactin secretion may be important for the regulation of the growth cycle, but that the role of changes in thyroid hormone secretion is unclear.